Breast cancer survivors are at increased risk for developing second primary cancers compared to the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer.
This retrospective cohort included 6,481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0?months). BMI at the first cancer was extracted from the medical record. Outcomes included 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor (ER)-positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics.
The mean age at initial breast cancer diagnosis was 61.2 (standard dscore the need for effective prevention strategies.The development of checkpoint blockade immunotherapy has transformed the medical oncology armamentarium. But, despite its favorable impact on clinical outcomes, immunotherapy benefits only a subset of patients, and a substantial proportion of these individuals eventually manifest resistance. Serious immune-related adverse events and hyper-progression have also been reported. It is therefore essential to understand the molecular mechanisms and identify the drivers of therapeutic response and resistance. In this review, we provide an overview of the current and emerging clinically relevant genomic biomarkers implicated in checkpoint blockade outcome. U.S. Food and Drug Administration-approved molecular biomarkers of immunotherapy response include mismatch repair deficiency/microsatellite instability and tumor mutational burden ?10 mutations/megabase. Investigational genomic-associated biomarkers for immunotherapy response include alterations of the following genes/associated pathways chromatin remodeling (ARID1A, PBRM1, SMARCA4, SMARCB1, BAP1), major histocompatibility complex, specific (e.g., ultraviolet, APOBEC) mutational signatures, T-cell receptor repertoire, PDL1, POLE/POLD1, and neo-antigens produced by the mutanome; those potentially associated with resistance include β2-microglobulin, EGFR, Keap1, JAK1/JAK2/interferon-gamma signaling, MDM2, PTEN, STK11, and Wnt/Beta-catenin pathway alterations. Prospective clinical trials are needed to assess the role of a composite of these biomarkers in order to optimize the implementation of precision immunotherapy in patient care.Variation in CYP2A6, the primary enzyme responsible for nicotine metabolism, is associated with nicotine dependence, cigarette consumption, and abstinence outcomes in smokers. The impact of CYP2A6 activity on nicotine reinforcement and tobacco cue-reactivity, mechanisms that may contribute to these previous associations, has not been fully evaluated.
CYP2A6 activity was indexed using three genetic approaches in 104 daily smokers completing forced-choice and cue-induced craving tasks assessing nicotine reinforcement and tobacco cue-reactivity, respectively. First, smokers were stratified by the presence or absence of reduced/loss of function CYP2A6 gene variants (normal vs. reduced metabolizers). As nicotine metabolite ratio (NMR) is a reliable biomarker of CYP2A6 activity, our second and third approaches used additional genetic variants identified in genome-wide association studies of NMR to create a weighted genetic risk score (wGRS) to stratify smokers (fast vs. slow metabolizers) and calculate a wGRS-der therapeutically or as a clinically relevant biomarker in a precision medicine approach, for tobacco use disorder treatment.
CYP2A6 activity is a key determinant of smoking behaviour and outcomes. Therefore, these findings support the targeting of CYP2A6 activity, either therapeutically or as a clinically relevant biomarker in a precision medicine approach, for tobacco use disorder treatment.In 2019, approximately, 1.4 billion people travelled internationally. Many individuals travel to megacities where air pollution concentrations can vary significantly. Short-term exposure to air pollutants can cause morbidity and mortality related to cardiovascular and respiratory disease, with the literature clearly reporting a strong association between short-term exposure to particulate matter ?2.5 μm and ozone with adverse health outcomes in resident populations. However, limited research has been conducted on the health impacts of short-term exposure to air pollution in individuals who travel internationally. The objective of this systematic review was to review the evidence for the respiratory and cardiovascular health impacts from exposure to air pollution during international travel to polluted cities in adults aged ?18 years old.
We searched PubMed, Scopus and EMBASE for studies related to air pollution and the health impacts on international travellers. Of the initially identified 115 articles that fit the search criteria, 6 articles were selected for the final review. All six studies found indications of adverse health impacts of air pollution exposure on international travellers, with most of the changes being reversible upon return to their home country/city. https://www.selleckchem.com/products/d34-919.html However, none of these studies contained large populations nor investigated vulnerable populations, such as children, elderly or those with pre-existing conditions.
More research is warranted to clearly understand the impacts of air pollution related changes on travellers' health, especially on vulnerable groups who may be at higher risk of adverse impacts during travel to polluted cities.
More research is warranted to clearly understand the impacts of air pollution related changes on travellers' health, especially on vulnerable groups who may be at higher risk of adverse impacts during travel to polluted cities.Growing international migration has increased the complexity of tuberculosis transmission patterns. Italy's decision to close its borders in 2018 made of Spain the new European porte entrée for migration from the Horn of Africa (HA). In one of the first rescues of migrants from this region at the end of 2018, tuberculosis was diagnosed in eight subjects, mainly unaccompanied minors.
Mycobacterium tuberculosis isolates from these recently arrived migrants were analysed by Mycobacterial Interspersed Repetitive-Unit/Variable-Number of Tandem Repeat (MIRU-VNTR) and subsequent whole genome sequencing (WGS) analysis. Data were compared with those from collections from other European countries receiving migrants from the HA and a strain-specific PCR was applied for a fast searching of common strains. Infections in a cellular model were performed to assess strain virulence.
MIRU-VNTR analysis allowed identifying an epidemiological cluster involving three of the eight cases from Somalia (0 single-nucleotide polymorphisms between isolates, HA cluster).